Mass Spectrometric Analysis Identifies AIMP1 and LTA4H as FSCN1-Binding Proteins in Laryngeal Squamous Cell Carcinoma
Mass Spectrometric Analysis Identifies AIMP1 and LTA4H as FSCN1-Binding Proteins in Laryngeal Squamous Cell Carcinoma
复制标题
质谱分析鉴定 AIMP1 和 LTA4H 为喉鳞状细胞癌中的 FSCN1 结合蛋白
DOI：
10.1002/pmic.201900059
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发表时间：
2019-07-26
期刊：
影响因子：
3.4
通讯作者：
Wang, Binquan
中科院分区：
文献类型：
--
作者：
Gao, Wei;An, Changming;Wang, Binquan
肌成束蛋白1（FSCN 1）的失调可增强喉鳞状细胞癌（LSCC）的细胞增殖、侵袭和运动，但其机制尚不清楚。在这里，免疫共沉淀和质谱法用于识别潜在的FSCN 1结合蛋白。FSCN 1结合蛋白的功能注释通过基因本体论和京都基因百科全书和基因组途径分析进行。进一步构建了FSNC 1结合蛋白的蛋白质-蛋白质相互作用网络，验证了FSNC 1与新发现的相互作用蛋白AIMP 1和LTA 4 H的相互作用。此外，AIMP 1和LTA 4 H在喉鳞状细胞癌中的表达和功能的作用进行了研究。共有123个蛋白被鉴定为潜在的FSCN 1结合蛋白，功能注释显示FSCN 1结合蛋白在致癌过程中显著富集，如丝状伪足组装调节和GT3活性。Co-IP/Western印迹和免疫荧光证实AIMP 1和LTA 4 H与FSCN 1结合并共定位。此外，AIMP 1和LTA 4 H在LSCC组织中均上调，并且AIMP 1或LTA 4 H的敲低抑制LSCC细胞增殖、迁移和侵袭。总的来说，FSCN 1结合伴侣的鉴定增强了对FSCN 1介导的恶性表型机制的理解，这些发现表明FSCN 1与AIMP 1和LTA 4 H结合可能促进LSCC的进展。
Dysregulation of fascin actin-bundling protein 1 (FSCN1) enhances cell proliferation, invasion, and motility in laryngeal squamous cell carcinoma (LSCC), while the mechanism remains unclear. Here, co-immunoprecipitation and mass spectrometry is utilized to identify potential FSCN1-binding proteins. Functional annotation of FSCN1-binding proteins are performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Furthermore, the protein-protein interaction network of FSNC1-binding proteins is constructed and the interactions between FSCN1 and novel identified interacting proteins AIMP1 and LTA4H are validated. Moreover, the expression and functional role of AIMP1 and LTA4H in LSCC are investigated. A total of 123 proteins are identified as potential FSCN1-binding proteins, and functional annotation shows that FSCN1-binding proteins are significantly enriched in carcinogenic processes, such as filopodium assembly-regulation and GTPase activity. Co-IP/western blotting and immunofluorescence confirm that AIMP1 and LTA4H bind and colocalize with FSCN1. Furthermore, both AIMP1 and LTA4H are upregulated in LSCC tissues, and knockdown of AIMP1 or LTA4H inhibits LSCC cell proliferation, migration, and invasion. Collectively, the identification of FSCN1-binding partners enhances understanding of the mechanism of FSCN1-mediated malignant phenotypes, and these findings indicate that FSCN1 binds to AIMP1 and LTA4H might promote the progression of LSCC.